This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cell migration is a superb example of biological complexity, as it intertwines biochemical signaling networks with biophysical locomotory processes. While the myriad of molecular components and interactions continue to become identified, the challenge looms to integrate them all into the operation of cell migration as a dynamical system. We are using the Virtual Cell (VC) environment to enable simulations of the locomotory process. The VC is already able to simulate reaction-diffusion equations on the 3-D domains (cellular interior) of complex geometries. Thus, numerical simulation and visualization of a sub-model are being developed that incorporate spatio-temporal dynamics of essential regulatory molecules in the cytoplasm. This includes reaction-diffusion equations describing chemical kinetics, diffusion and transport of actin monomers, actin binding proteins and ions. As the next step, we are enabling VC to solve the reaction-advection-diffusion equations of cytoskeletal mechanics and adhesive system on the 3-D domains and their boundaries, respectively. In addition to incorporating the appropriate numerics infrastructure to deal with the new mathematical formalisms, a key challenge will be to develop graphical representations of the biophysics that can be deployed by the user to fully specify models within a mechanics-enabled problem domain. Such representations would be structured in terms of easily manipulatable sets of components consisting of the structures, molecules, and relevant interactions. Finally, we will expand the VC software in order to dynamically change the cellular geometry to account for the protrusion/retraction movements of the cellular surface. We will adapt finite element techniques to problems of cytoskeletal dynamics with changing geometries.